1. Field of the Invention
The present invention relates to a genetic test for bladder cancer by analyzing a chromosome.
2. Background Art
It has been reported that when canceration of the bladder cells occurs, a loss in a chromosome takes place, and consequently loss of heterozygosity (LOH) frequently occurs at 4p, 8p, 9p, 9q, 11p and 17p sites (see nonpatent documents 1 to 5). Therefore, bladder cancer can be effectively tested by detecting LOH. However, this method uses the tissue cells excised from bladder cancer, and therefore, a more simplified method has been strongly desired.
The patent document 1 discloses a method of testing bladder cancer by analyzing LOH of Chromosome 9 using nucleic acids recovered from the urine of an early-stage bladder cancer patients. In this test method, a deletion in chromosome 9 is detected by using a single nucleotide polymorphism (SNP) and a microsatellite type polymorphic site which differs in number of repeat units by one or more, in the short arm (9p) and the long arm (9q) of Chromosome 9. More specifically, after the region having a genetic polymorphism on Chromosome 9 is amplified by PCR, the resultant PCR product is blunted, and the obtained nucleic acid fragment is analyzed by a single-strand conformation polymorphism (SSCP) to detect LOH at a site of genetic polymorphism.    Nonpatent document 1    Cancer Res. 54, p 784-788, Spruck III et al. (1994)    Nonpatent document 2    Cancer Genet. Cytogenet., 77 p 118-124, Matsuya et al. (1994)    Nonpatent document 3    Lancet 342, p 469-471, Dalbagni et al. (1993)    Nonpatent document 4    Cancer Res. 54, p 531-538, Knowles et al. (1994)    Nonpatent document 5    Cancer Res. 50, p 7081-7083, Olumi et al. (1990)    Patent document 1    JP Patent Publication (Kokai) No. 11-341999
In the test method of the patent document 1, since the frequency of occurrence of heterozygotes is low at a site of genetic polymorphism within the region of the VAV2 gene used near the end of the long arm (9q32 to q34.3), analysis of LOH cannot be performed in some cases. For this reason, in a conventional bladder cancer test, it is difficult to identify a deletion in a chromosome near the end of the long arm, which raises a problem that such a test cannot be performed efficiently.
Accordingly, the present invention is directed to efficiently identifying a deletion in a chromosome 9 near the end of the long arm.